rs878077

Variant names:

• chr14-100148786-G-A
• rs878077
• NM_206918.3:c.825+182C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_206918.3(DEGS2):​c.825+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 152,354 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.023 (64 hom., cov: 35)
• Consequence: DEGS2 NM_206918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• Publications: 1 publications found

Genes affected

DEGS2 (HGNC:20113): (delta 4-desaturase, sphingolipid 2) This gene encodes a bifunctional enzyme that is involved in the biosynthesis of phytosphingolipids in human skin and in other phytosphingolipid-containing tissues. This enzyme can act as a sphingolipid delta(4)-desaturase, and also as a sphingolipid C4-hydroxylase. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0233 (3549/152354) while in subpopulation NFE AF = 0.0344 (2342/68030). AF 95% confidence interval is 0.0333. There are 64 homozygotes in GnomAd4. There are 1703 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEGS2	NM_206918.3	c.825+182C>T		intron_variant	Intron 2 of 2	ENST00000305631.7	NP_996801.2
DEGS2	XM_006720043.4	c.717+182C>T		intron_variant	Intron 3 of 3		XP_006720106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEGS2	ENST00000305631.7	c.825+182C>T		intron_variant	Intron 2 of 2	1	NM_206918.3	ENSP00000307126.5
DEGS2	ENST00000553834.1	c.83-1879C>T		intron_variant	Intron 1 of 1	3		ENSP00000450637.1
DEGS2	ENST00000557117.1	n.*199C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3550 AN: 152236 Hom.: 64 Cov.: 35

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0233 AC: 3549 AN: 152354 Hom.: 64 Cov.: 35 AF XY: 0.0229 AC XY: 1703 AN XY: 74500

African (AFR) AF: 0.00591 AC: 246 AN: 41592

American (AMR) AF: 0.0274 AC: 420 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5188

South Asian (SAS) AF: 0.00310 AC: 15 AN: 4832

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0344 AC: 2342 AN: 68030

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0219 Hom.: 16

Bravo AF: 0.0227

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.70
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs878077; hg19: chr14-100615123;